While most people may have difficulty distinguishing a
person from his or her mirror image, proteins in cells have
no such problem. They are exquisitely selective, able to
latch on tightly to one molecule but reject its mirror
image.

Now scientists claim that a 50-year-old theory explaining
how proteins and enzymes discriminate so precisely,
considered gospel by most researchers, needs revision.

The finding could significantly help drug designers, who
may needlessly be discarding good drug candidates because of
this misconception.

"The reigning theory of how enzymes distinguish between
very slight differences in molecules is the three-point
attachment model found in essentially all biochemistry
textbooks," said Daniel Koshland Jr., professor of molecular
and cell biology and a researcher in the Center for Advanced
Materials at Lawrence Berkeley National Laboratory.

"This is very important in pharmacology, where drug
designers rely on the theory to design a particular mirror
image, or enantiomer, to fit exactly into the active site of
an enzyme or receptor. Well, the classic explanation needs
correction."

Koshland and Andrew Mesecar, a former postdoctoral fellow
at Berkeley and now an assistant professor at the University
of Illinois, Chicago, argue that the model that explains how
proteins bind to other molecules must be changed.

These models explain how proteins bind to "chiral"
molecules, that is, molecules that cannot be superimposed on
their mirror image. Typically the mirror-image versions act
very differently in the body. Some bacteria can degrade one
version of a pollutant but not its mirror image; a key
receptor in the brain is turned on by an amino acid but not
its mirror image